May 9, 2013

Herpes Vaccine Could Arise Due To Suppressive Immune Cell Discovery

Herpes is an infectious disease that affects more than 24 million people in the United States alone, according to a recent report by the US Centers for Disease Control and Prevention (CDC). Now, researchers have identified a class of immune cells that exist in genital skin and mucosa that may play a role in developing a vaccine to prevent one of the most common sexually transmitted infections (STIs) in America.

These immune cells, known as CD8Î±Î±+ T cells, have been found to suppress symptoms and recurring outbreaks of genital herpes, and are believed to be the key reason most sufferers are asymptomatic when viral reactivations occur. The researchers, from Fred Hutchinson Cancer Research Center (FHCRC) and University of Washington (U-W), say the immune cells could open up a new path in the prevention and treatment of herpes simplex virus type 2 (HSV-2). The team said that identifying these T cells´ specific molecular targets (epitopes) will be the next step in developing a vaccine.

The researchers, led by Larry Corey, MD, virologist and president of FHCRC, also believe that better understanding of these T cells could play a crucial role in the development of vaccines for other types of skin and mucosal infections, including HIV infection.

"The discovery of this special class of cells that sit right at the nerve endings where HSV-2 is released into skin is changing how we think about HSV-2 and possible vaccines," said Corey in a statement. "For the first time, we know the type of immune cells that the body uses to prevent outbreaks. We also know these cells are quite effective in containing most reactivations of HSV-2. If we can boost the effectiveness of these immune cells we are likely to be able to contain this infection at the point of attack and stop the virus from spreading in the first place.”

Currently there is no treatment that can cure genital herpes, but antiviral medications have been shown to prevent or shorten recurring outbreaks while a person is taking the medication. But even with antiviral treatment, Corey noted that the virus “often breaks through this barrier and patients still can transmit the infection to others.”

"In addition, newborn herpes is one of the leading infections transmitted from mothers to children at the time of delivery. An effective genital herpes vaccine is needed to eliminate this complication of HSV-2 infection," he added.

Jia Zhu, PhD, a corresponding author on the study from U-W´s Laboratory of Medicine, said the long-term presence of CD8Î±Î±+ T cells where initial infection occurs could explain why patients have asymptomatic recurrences because the cells constantly recognize and destroy the virus.

"The cells we found perform immune surveillance and contain the virus in the key battlefield where infection occurs, which is the dermal-epidermal junction," said Zhu, who is also an affiliate investigator at FHCRC. "These cells are persistent in the skin and represent a newly discovered phenotype distinguished from those of CD8+ T cells circulating in the blood."

The team explained that the dermal-epidermal junction (DEJ) — region where the tissue layers connect to the outer skin layer — is an important area because of the roles it plays in cellular communication, nutrient exchange and absorption. The team further explained that T cell activity in the DEJ is important because this is the region where genital herpes virus multiplies after traveling from the body´s sensory neurons where the virus hides. The team found in earlier research that nerve endings that reach the DEJ are able to release the virus into the skin, where it can cause lesions.

Prior to the discovery of T cells in skin, these immune cells were only found in gut mucosa. Previous research has mainly focused on studying these cells in blood.

"We did not expect to find CD8Î±Î±+ T cells in the skin," Zhu said. "This was a surprise."

The researchers used a novel technique to examine the T cells in human skin tissue. Zhu noted that this technique could provide a “roadmap” to the treatment of other human diseases. She added that the studies they performed were unique.

“To our knowledge, we are the only research group to use sequential human biopsies to study CD8+ T cell function in situ, in their natural spatial distribution and at their original physiological state,” said Zhu.

With a disease that affects more than 775,000 people in the US every year, finding a vaccine that can prevent and/or cure herpes will be pretty significant. According to a CDC fact sheet, about one in six people aged 14 to 49 have genital HSV-2. The most common transmission of the infection is through sexual contact with someone who has the disease. Transmission can even occur when the partner shows no visible sores.

While the CDC notes that use of condoms can reduce the risk of genital herpes, the surest way to avoid transmission of the virus is to abstain from sexual contact because infection can occur in both male and female genital areas that are not covered or protected by a latex condom. To ensure it is safe to have sex, partners can seek testing to determine if they are infected with HSV.

Most individuals infected with HSV-1 or HSV-2 experience either no symptoms or have very mild symptoms that can go unnoticed or mistaken for other skin conditions. Because of this, most people infected with HSV are not aware of their infection.

The research team said the T cells examined could also play a role in helping in the treatment of herpes that affects oral regions, but they only examined the cells´ role in genital herpes for this study.

The team´s study findings are described in the May 8 advance online edition of the journal Nature.